Palladin is overexpressed in the non-neoplastic stroma of infiltrating ductal adenocarcinomas of the pancreas, but is only rarely overexpressed in neoplastic cells
Background: It has recently been suggested that over expression of palladin in sporadic pancreatic cancer may contribute to pancreatic cancer’s invasive and migratory abilities. This hypothesis was based on reverse transcriptase-polymerase chain reaction analyses of bulk pancreatic tissue, yet pancr...
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Published in | Cancer biology & therapy Vol. 6; no. 3; pp. 324 - 328 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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United States
01.03.2007
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Abstract | Background: It has recently been suggested that over expression of palladin in sporadic pancreatic cancer may contribute to pancreatic cancer’s invasive and migratory abilities. This hypothesis was based on reverse transcriptase-polymerase chain reaction analyses of bulk pancreatic tissue, yet pancreatic cancer is a complex admixture of neoplastic epithelial cells and desmoplastic stroma.
Design: Immunohistochemical labeling of tissue microarrays was used to define the patterns of palladin protein expression in 177 ductal adenocarcinomas of the pancreas. Western blot analysis was used to determine the epitope(s) of palladin recognized by the antibody as well as the relative levels of palladin expression in short-term cultures of stromal fibroblasts, non-neoplastic ductal cells and pancreatic cancer cell lines.
Results: Immunolabeling revealed that the palladin protein was strongly over expressed in non-neoplastic stromal cells in 171 (96.6%) of the 177 evaluable pancreatic cancers. By contrast, the over expression of palladin protein by the neoplastic epithelial cells relative to normal pancreatic epithelium was observed in only 22 (12.4%) of the 177 cancers. Western blot analysis confirmed that the antibody recognizes the ~90 kDa isoform of palladin, and demonstrated that fibroblast cell lines had higher expression of palladin than pancreatic cancer cell lines.
Conclusions: The over expression of palladin relative to normal pancreas in the majority of pancreatic cancers is limited to non-neoplastic stromal cells. This observation highlights the limitations of relying on bulk tissues when analyzing gene expression. Since palladin is not over expressed in most pancreatic cancer cells, the over expression of palladin is not likely to be responsible for pancreatic cancer cells invasive and migratory abilities. |
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AbstractList | It has recently been suggested that overexpression of palladin in sporadic pancreatic cancer may contribute to pancreatic cancer's invasive and migratory abilities. This hypothesis was based on reverse transcriptase-polymerase chain reaction analyses of bulk pancreatic tissue, yet pancreatic cancer is a complex admixture of neoplastic epithelial cells and desmoplastic stroma.
Immunohistochemical labeling of tissue microarrays was used to define the patterns of palladin protein expression in 177 ductal adenocarcinomas of the pancreas. Western blot analysis was used to determine the epitope(s) of palladin recognized by the antibody as well as the relative levels of palladin expression in short-term cultures of stromal fibroblasts, non-neoplastic ductal cells and pancreatic cancer cell lines.
Immunolabeling revealed that the palladin protein was strongly overexpressed in non-neoplastic stromal cells in 171 (96.6%) of the 177 evaluable pancreatic cancers. By contrast, the overexpression of palladin protein by the neoplastic epithelial cells relative to normal pancreatic epithelium was observed in only 22 (12.4%) of the 177 cancers. Western blot analysis confirmed that the antibody recognizes the -90 kDa isoform of palladin, and demonstrated that fibroblast cell lines had higher expression of palladin than pancreatic cancer cell lines.
The overexpression of palladin relative to normal pancreas in the majority of pancreatic cancers is limited to non-neoplastic stromal cells. This observation highlights the limitations of relying on bulk tissues when analyzing gene expression. Since palladin is not overexpressed in most pancreatic cancer cells, the overexpression of palladin is not likely to be responsible for pancreatic cancer cells invasive and migratory abilities. BACKGROUNDIt has recently been suggested that overexpression of palladin in sporadic pancreatic cancer may contribute to pancreatic cancer's invasive and migratory abilities. This hypothesis was based on reverse transcriptase-polymerase chain reaction analyses of bulk pancreatic tissue, yet pancreatic cancer is a complex admixture of neoplastic epithelial cells and desmoplastic stroma. DESIGNImmunohistochemical labeling of tissue microarrays was used to define the patterns of palladin protein expression in 177 ductal adenocarcinomas of the pancreas. Western blot analysis was used to determine the epitope(s) of palladin recognized by the antibody as well as the relative levels of palladin expression in short-term cultures of stromal fibroblasts, non-neoplastic ductal cells and pancreatic cancer cell lines. RESULTSImmunolabeling revealed that the palladin protein was strongly overexpressed in non-neoplastic stromal cells in 171 (96.6%) of the 177 evaluable pancreatic cancers. By contrast, the overexpression of palladin protein by the neoplastic epithelial cells relative to normal pancreatic epithelium was observed in only 22 (12.4%) of the 177 cancers. Western blot analysis confirmed that the antibody recognizes the -90 kDa isoform of palladin, and demonstrated that fibroblast cell lines had higher expression of palladin than pancreatic cancer cell lines. CONCLUSIONSThe overexpression of palladin relative to normal pancreas in the majority of pancreatic cancers is limited to non-neoplastic stromal cells. This observation highlights the limitations of relying on bulk tissues when analyzing gene expression. Since palladin is not overexpressed in most pancreatic cancer cells, the overexpression of palladin is not likely to be responsible for pancreatic cancer cells invasive and migratory abilities. Background: It has recently been suggested that over expression of palladin in sporadic pancreatic cancer may contribute to pancreatic cancer’s invasive and migratory abilities. This hypothesis was based on reverse transcriptase-polymerase chain reaction analyses of bulk pancreatic tissue, yet pancreatic cancer is a complex admixture of neoplastic epithelial cells and desmoplastic stroma. Design: Immunohistochemical labeling of tissue microarrays was used to define the patterns of palladin protein expression in 177 ductal adenocarcinomas of the pancreas. Western blot analysis was used to determine the epitope(s) of palladin recognized by the antibody as well as the relative levels of palladin expression in short-term cultures of stromal fibroblasts, non-neoplastic ductal cells and pancreatic cancer cell lines. Results: Immunolabeling revealed that the palladin protein was strongly over expressed in non-neoplastic stromal cells in 171 (96.6%) of the 177 evaluable pancreatic cancers. By contrast, the over expression of palladin protein by the neoplastic epithelial cells relative to normal pancreatic epithelium was observed in only 22 (12.4%) of the 177 cancers. Western blot analysis confirmed that the antibody recognizes the ~90 kDa isoform of palladin, and demonstrated that fibroblast cell lines had higher expression of palladin than pancreatic cancer cell lines. Conclusions: The over expression of palladin relative to normal pancreas in the majority of pancreatic cancers is limited to non-neoplastic stromal cells. This observation highlights the limitations of relying on bulk tissues when analyzing gene expression. Since palladin is not over expressed in most pancreatic cancer cells, the over expression of palladin is not likely to be responsible for pancreatic cancer cells invasive and migratory abilities. |
Author | Michel M. Ouellette Richard D. Schulick Anirban Maitra Ralph Hruban Safia N. Salaria Peter Illei James R. Eshleman Kimberly M. Walter Jordan M. Winter Michael Goggins Rajni Sharma Alison Klein |
AuthorAffiliation | 5 Eppley Institute for Research in Cancer, The University of Nebraska Medical Center, Omaha, Nebraska USA 2 The Sol Goldman Pancreatic Cancer Research Center; Department Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland USA 4 Institute for Genetic Medicine and Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland USA 1 The Sol Goldman Pancreatic Cancer Research Center; Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland USA 3 Department of Epidemiology, The Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland USA |
AuthorAffiliation_xml | – name: 1 The Sol Goldman Pancreatic Cancer Research Center; Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland USA – name: 3 Department of Epidemiology, The Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland USA – name: 4 Institute for Genetic Medicine and Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland USA – name: 2 The Sol Goldman Pancreatic Cancer Research Center; Department Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland USA – name: 5 Eppley Institute for Research in Cancer, The University of Nebraska Medical Center, Omaha, Nebraska USA |
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Snippet | Background: It has recently been suggested that over expression of palladin in sporadic pancreatic cancer may contribute to pancreatic cancer’s invasive and... It has recently been suggested that overexpression of palladin in sporadic pancreatic cancer may contribute to pancreatic cancer's invasive and migratory... BACKGROUNDIt has recently been suggested that overexpression of palladin in sporadic pancreatic cancer may contribute to pancreatic cancer's invasive and... |
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SubjectTerms | Adenocarcinoma - chemistry Adenocarcinoma - metabolism Adenocarcinoma - pathology Aged Binding Biology Bioscience Blotting, Western Calcium Cancer Carcinoma, Pancreatic Ductal - chemistry Carcinoma, Pancreatic Ductal - metabolism Carcinoma, Pancreatic Ductal - pathology Cell Cycle Cytoskeletal Proteins - analysis Cytoskeletal Proteins - genetics Cytoskeletal Proteins - metabolism Female Humans Immunohistochemistry Landes Male Neoplasm Invasiveness Organogenesis Pancreas - chemistry Pancreas - metabolism Pancreas - pathology Pancreatic Neoplasms - chemistry Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Phosphoproteins - analysis Phosphoproteins - genetics Phosphoproteins - metabolism Proteins RNA, Messenger - analysis RNA, Messenger - metabolism Stromal Cells - chemistry Stromal Cells - metabolism Tissue Array Analysis Up-Regulation |
Title | Palladin is overexpressed in the non-neoplastic stroma of infiltrating ductal adenocarcinomas of the pancreas, but is only rarely overexpressed in neoplastic cells |
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